Structural Insights into Microbial One-Carbon Metabolic Enzymes Ni-Fe-S-Dependent Carbon Monoxide Dehydrogenases and...

Ni-Fe-S-dependent carbon monoxide dehydrogenases (CODHs) are enzymes that interconvert CO and CO₂ by using their catalytic Ni-Fe-S C-cluster and their Fe-S B- and D-clusters for electron transfer. CODHs are important in the microbiota of animals such as humans, ruminants, and termites because they can facilitate the use of CO and CO₂ as carbon sources and serve to maintain redox homeostasis. The bifunctional carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) is responsible for acetate production via the Wood-Ljungdahl pathway, where acetyl-CoA is assembled from two CO₂-derived one-carbon units. A Ni-Fe-S A-cluster is key to this chemistry. Whereas acetogens use the A- and C-clusters of CODH/ACS to produce acetate from CO₂, methanogens use A- and C-clusters of an acetyl-CoA decarbonylase/synthase complex (ACDS) to break down acetate en route to CO₂ and methane production. Here we review some of the recent advances in understanding the structure and mechanism of CODHs, CODH/ACSs, and ACDSs, their unusual metallocofactors, and their unique metabolic roles in the human gut and elsewhere.